Hedgehog Genes and Human Brain Development
Posted February 28, 1999
By Chris Kapicka PhD
Once a sperm fertilizes an egg, development of the embryo begins. As the embryo's cells continue to divide and grow, some cells are triggered to become limbs, whereas
others become the brain, kidneys, liver, and all other organs. How do an embryo's cells know which structure to form? Embryologists have been trying to answer this question for decades.
With the advances in molecular genetic techniques, such as gene cloning, scientists have begun to find some of the answers to this basic question.
Biologists now know that the same or similar genes shape the development of comparable structures across the animal kingdom - from insects to humans. One group of
genes, called the homeobox or Hox genes, guides the early development of the head and tail end of the embryo. First discovered in fruit flies, similar homeobox genes have been
discovered in various animals, including humans.
Over the last few years, it appears that groups of genes in "nature's toolbox of genes" appear over and over again in many animals. In the 1980s, a gene that controls
a protein important in the process of limb and brain development was discovered in fruit flies. This protein was called hedgehog protein because fruit flies with the mutant hedgehog
gene rolled up and were bristly, like a frightened hedgehog. Scientists searched for this gene in other vertebrates (mice, chicken, fish, and humans) and have found at least three similar
versions of the hedgehog gene. One similar gene they called the sonic hedgehog gene has been linked to the generation of patterns in the cells of the human brain and spinal
cord.
The gene for sonic hedgehog protein is found on human chromosome number 7. Since its discovery, this gene has become one of the most studied genes in all of biology.
The protein is important in determining the bilateral nature of the human brain. This protein also is important in guiding the arrangement of fingers and toes in their proper sequences.
Very early in the human embryo, the notochord cells produce the hedgehog protein. The cells adjacent to the notochord receive large amounts of hedgehog protein. These
cells develop into support cells of the nervous system. Farther away from the notochord, only small amounts of hedgehog protein makes it to the cells, which become motor nerve cells
that control movement. Thus, this hedgehog protein gradient has been shown to control the fate of the cells surrounding the notochord in the embryo.
A link between the hedgehog gene and a human disorder has been discovered. A defect in the sonic hedgehog gene causes holoprosencephaly in humans, the
most common congenital forebrain defect. This disorder occurs in one in 16,000 live births. Defects caused by this disorder range from malformation of the upper lip and/or nose in less
severe forms to major structural defects of the head and brain in severe forms. Further research is beginning to sort out how mutations of this gene result in the different severities
of this disorder.
Activity
After reading about the homeobox genes common to several vertebrate groups, explore the following web sites on genetic defects. Using this information, state
your own views on how the discovery of genes that control the development of various organs in the human body should be used. Should all embryos have genetic screenings to determine
if they carry any correctable defects? Should physicians be allowed to insert the correct gene for development when an embryo has been found to carry a genetic defect?
References
McGinnis, William and Michael Kuziora. "The Molecular Architects of Body Design" Scientific American, February, 1994.
Riddle, Robert D and Clifford J. Tabin. "How Limbs Develop" Scientific American, February, 1999, pp. 74-79.
Snustad, D. Peter, Michael J. Simmons, and John B.Jenkins. Principles of Genetics New York: John Wiley & Sons, Inc. 1997.
Web Sites
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